Non-thrombogenic stent jacket

ABSTRACT

Disclosed is the use of serous tissue, such as pericardium, as a component of intracorporeal implants. Particularly, disclosed is a jacketed stent assembly comprising an expandable stent provided with a jacket of processed serous tissue which, in some embodiments, is impregnated with a therapeutic or diagnostic agent. In a preferred embodiment, the jacket of the expandable stent is formed of pericardial tissue, preferably bovine or porcine pericardial tissue.

This application is a Continuation of U.S. patent application Ser. No.11/181,978, filed on Jul. 15, 2005, which is a Continuation-In-Part(CIP) of U.S. patent application Ser. No. 09/716,038, filed on Nov. 17,2000, now abandoned, which is a Continuation of U.S. patent applicationSer. No. 09/156,034, filed on Sep. 17, 1998, now U.S. Pat. No.6,254,627, issued on Jul. 3, 2001, which is a Continuation-In-Part (CIP)of U.S. patent application Ser. No. 09/053,200, filed on Apr. 1, 1998,now abandoned, which is a Continuation-In-Part (CIP) of U.S. patentapplication Ser. No. 09/035,114, filed on Mar. 4, 1998, now abandoned,which is a Continuation-In-Part (CIP) of U.S. patent application Ser.No. 09/005,972, filed on Jan. 12, 1998, now abandoned, which is aContinuation-In-Part (CIP) of U.S. patent application Ser. No.08/935,784, filed on Sep. 23, 1997, now U.S. Pat. No. 6,468,300, issuedon Oct. 22, 2002.

The above applications are all hereby incorporated by reference as iffully set forth herein.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to the field of medicine, and moreparticularly to the field of intracorporeal devices such as stents. Thepresent invention also relates to the field of expandable intraluminalsupport devices such as stents and the like.

Typically, stents are expandable, tubular metallic devices that arepositioned within a patient's vasculature or other body lumen andexpanded in order to support a vessel or body lumen and allow the flowof blood or other body fluids therethrough. Often, the stents are formedfrom a deformable metal and delivered to a desired intraluminal locationusing a balloon-type catheter. By advancing the catheter through thebody lumen, the stent may be delivered to a desired position. Inflatingthe balloon then deforms the stent into an expanded configuration,seating it within the artery or other body lumen. Other implementationsmake use of a self-expanding stent formed from a suitable material suchas pseudoelastic material that is delivered in a constricted conditionand when released spontaneously expands to an enlarged configuration. Inother embodiments, a stent made of shape memory alloy (e.g. NiTi alloy)is inserted into the body lumen in a martensitic phase and transforms toan austenite phase which has an expanded memory when raised to atemperature above the transformation temperature, usually less than 45°C.

Stents are often used in conjunction with an intravascular treatment forobstructive coronary artery disease. For example, ablation, atherectomy,balloon dilation, laser treatment or other procedures are among themethod used to widen a stenotic region of a patient's vasculature.However, restenosis occurs in large percentage of percutaneoustransluminal coronary angioplasty (PTCA) patients and rates can be evenhigher with other procedures. The prior art has employed a number ofmechanical and pharmacological strategies to reduce the restenosis rate,but none have been particularly effective. Accordingly, stents have beenproposed to maintain the patency of a treated vessel and preventrestenosis. Using stents, restenosis rates have fallen to less than 20%.

Restenosis is thought to be a natural healing reaction provoked byinjury from the intravascular procedure. The healing process frequentlycauses thrombosis and may lead to intimal hyperplasia that occludes thevessel. Although helpful in reducing restenosis, stents do not representa complete solution. The framework of the stent may still allowmigration and proliferation of the smooth muscle cells, while the stentitself can be thrombogenic. To address these problems, stents have beencovered with DACRON, PTFE and autologous vein and the surface has beenseeded with endothelial cells or otherwise treated. Each of thesesolutions suffer from certain drawbacks, such as not beingbiocompatible, lacking sufficient mechanical strength, having a surfacethat is difficult to prepare, lack of ready availability and beingthrombogenic.

Antithrombotic drug regimens, in which anticoagulants and thrombolyticagents are administered during and after deployment of the stent, havealso been employed to reduce the risk of thrombosis.

In the art it is known to cover stents with jackets made of serousmembrane.

Serous membrane is a type of tissue that holds various organs togetherand include the peritoneum (the serous membrane that lines the cavity ofthe abdomen of a mammal and is folded inward over the abdominal andpelvic viscera), the pericardium (the conical sac of serous membranethat encloses the heart and the roots of the great blood vessels) andthe pleura (the serous membrane that lines each half of the thorax andis folded back over the surface of the lung of the same side). Theserous membranes release a lubricating serous fluid allowing theexpanding and contracting organs (including the lungs) held within agiven serous membrane to slide gently against adjacent parts of thebody.

Serous membranes are made of two strata of tissue. The serous stratum orlayer of a serous membrane is a very smooth single layer of flattened,nucleated mesothelial cells united at their edges by cement substance.The serous layer is the side that faces towards and contacts the organs.The serous cells secrete the lubricating serous fluid. The serous cellsrest on a basement layer or stratum (also called the subserous areolartissue), a rough, strong fibrous layer that forms a protective sackabout the serous layer. Beneath the basement membrane are networks ofyellow elastic and white fibers imbedded in ground substance that alsocontains connective-tissue cells.

The use of serous membranes as a component of intracorporeal implants isknown in the art.

In U.S. Pat. No. 4,502,159 is taught a method for preparing a tubulargraft from pericardium.

In U.S. Pat. No. 5,782,914 is taught a method for processing animaltissue such as serous membranes for use as a graft material inintracorporeal implants.

In U.S. Pat. No. 5,934,283 is taught the use of tissues, includingserous tissues such as pericardium, peritoneum and tunica vaginalis infashioning a pubovaginal sling.

In U.S. Pat. No. 5,865,723 and in PCT Patent Application No.PCT/US96/20868 published as WO 97/24081 is discussed that vascularprostheses of autologous pericardial membrane fashioned into tubulargrafts have been used but have been proven to be ineffective, forexample as the pericardial membrane is subject to rupture and structuralfailure. Therefore in WO 97/24081 is taught a stent assembly comprisingpericardial, fascial rectus sheath or venous tissue formed as a jacketover a stent. The tissue is harvested, usually but not necessarilytreated in a stabilizing medium, and attached to the outside of thestent by rolling over the stent so that the two edges of the tissueoverlap by at least 35° (and preferably are wrapped twice about thestent) so as to obviate the need for sutures.

Due to the overlapping layers of pericardium, stent assemblies jacketedin accordance with the teachings of WO 97/24081 are quite thick, causinga significant reduction in the bore size of a bodily vessel in whichdeployed, limiting such stent assemblies for deployment only torelatively large bore lumina. Further, the thickness of a stent jacketmade in accordance with the teachings of WO 97/24081 reduces theflexibility and consequently maneuverability of such a stent assembly,limiting the locations in which such stents can be deployed.

In PCT Patent Application No. PCT/US96/13907 published as WO 97/09006 istaught a stent assembly comprising a jacket of at least one layer ofpericardial tissue (preferably human, bovine or porcine origin) coveringat least a portion of the inside or outside surface of a stent. Thethickness of the jacket is adjusted by varying the number of layers ofpericardium. The disadvantages of such stent assemblies are similar tothose of WO 97/24081.

Thus, there is a need for a stent capable of minimizing restenosis whilehaving a consistency similar to the native artery, a non-thrombogenicsurface and sufficient mechanical strength as well as beingbiocompatible and readily available.

It would be highly advantageous to have a material for use as acomponent in intracorporeal implants such as stents not having at leastsome of the disadvantages of the prior art.

SUMMARY OF THE INVENTION

The advantages of the teachings of the present invention are clear toone skilled in the art upon perusal of the description herein. Theteachings of the present invention provide a processed serous membranethat can be used as a component in intracorporeal implants such asstents having many advantages of the previously-used serous membranesyet is thinner. The fact that the processed serous membrane of thepresent invention is thin yet sufficiently flexible and strong allowsthe production of smaller and finer intracorporeal implants thanpreviously known. In the field of stents this is exceptionally importantas it allows the deployment of stents in smaller blood vessels, allowsthe use of smaller deployment catheters, provides a much more flexiblecovered stent to maneuver inside the cardiovascular network and reducesthe bore of a vessel in which deployed to a less significant degree thenheretofore known. Further, the unexpected flexibility and strength ofthe processed serous membrane of the present invention allows theproduction of stent assemblies including a jacket and a self-expandingstent or of stents that are balloon expandable at low pressures,something that was heretofore difficult if not impossible.

The invention is a stent assembly suitable for maintaining the patencyof a bodily lumen, generally comprising an expandable, tubular frameworkcomprising a stent at least in part within a cylinder of biocompatible,non-thrombogenic expandable material such as heterologous tissue.

Preferably, the heterologous tissue comprises bovine pericardium, butother preferred embodiments include porcine pericardium, aortic leafletand other suitable heterologous tissue. The expandable, tubularframework may be a conventional metallic stent. The stent may be anexpandable, tubular framework and may be a conventional self-expandingor balloon expandable stent. The jacket is disposed about either or bothof the outer and inner surfaces of the stent. In a preferred embodiment,the jacket is generally cylindrical for corresponding to the tubularframework or the stent.

This invention is also directed to a method for maintaining the patencyof a bodily lumen comprising the steps of mounting a stent assembly of atubular expandable, metallic framework forming the stent coaxiallydisposed within a cylinder of biocompatible, non-thrombogenic expandablematerial such as heterologous tissue on an expandable member on thedistal extremity of a catheter; advancing the catheter through thebodily lumen until the stent assembly is positioned at a desiredlocation; expanding the stent assembly by expanding the expandablemember onto which the stent assembly is mounted to anchor it within thebodily lumen; contracting the expandable member, e.g. deflating theballoon, and withdrawing the catheter. The expanded cylinder ofbiocompatible, non-thrombogenic expandable material such as heterologoustissue should extend over a substantial portion, preferably all, of thestenotic region in which it is disposed.

This invention is also directed to a method for maintaining the patencyof a bodily lumen generally comprising providing a delivery catheterhaving an expandable member on the distal extremity thereof, mountingthe stent assembly, including a tubular stent with a jacket ofbiocompatible, non-thrombogenic expandable material such as heterologoustissue disposed about at least part of the stent, on the expandablemember on the distal extremity of the delivery catheter. The catheter isadvanced through the body lumen within the patient until the distalextremity of the catheter having the stent assembly is positioned at adesired location therein. The stent assembly is expanded by expandingthe expandable member onto which the stent assembly is mounted to anchorthe stent assembly within the body lumen. Once the stent assembly iseffectively positioned within the body lumen, the expanded expandablemember may be contracted, e.g. by deflating the balloon, and then thedelivery catheter may be withdrawn.

A presently preferred embodiment of the invention is directed to a stentassembly suitable for expansion within a body lumen and delivery of atherapeutic or diagnostic agent therein, generally comprising anexpandable stent and an expandable, biocompatible, non-thrombogenicjacket such as heterologous tissue, which contains the therapeutic ordiagnostic agent and which is disposed about the expandable stent. Thejacket releasably contains at least one therapeutic or diagnostic agent.

A wide variety of therapeutic or diagnostic agents for a variety ofindications can be used, including angiogenesis agents, chemotherapeuticagents, antibiotic/antirejection agents and antithrombotic agents. Theterm “antithrombotic agents” is meant to include various agents forreducing the risk of thrombosis, including anticoagulants such asheparin, thrombolytic agents such as urokinase, streptokinase, tissueplasminogen activator (Actilyset), monoclonal antibodies such asAbeiximab (ReoPro), fibrinolytic agents, and the like. Angiogenesisagents that stimulate the growth of neo-vessels include agents such asbasic Fibroblast Growth Factor (bFGF) and Vascular Endothelial GrowthFactor (VEGF). Chemotherapeutic agents include agents such as Paclitaxel(Taxol®). Antibiotic/anti-rejection agents include agents such asSirolimus (Rapamune®).

In a presently preferred embodiment, the jacket is impregnated with aliquid containing the therapeutic or diagnostic agent. For example, ajacket formed from heterologous tissue which is submerged in a solutionof the therapeutic agent will absorb the solution. A variety of suitablemethods of applying the agent to the jacket may be used, including usingelectrodeposition, heat and pressure. Thereafter, the stent assembly canbe positioned at a desired site within the patient's body lumen, wherethe jacket will release the therapeutic agent. The jacket on the stentassembly may be impregnated just before use, or alternatively, stored inthe therapeutic or diagnostic agent so that the stent assembly ispreimpregnated.

The invention is also directed to a method for delivery of a therapeuticor diagnostic agent within a body lumen. The stent assembly including atubular stent with a jacket of biocompatible, non-thrombogenicexpandable material, such as heterologous tissue, containing atherapeutic or diagnostic agent is positioned within the body lumen asoutlined above. With the stent assembly positioned at a desiredlocation, the therapeutic or diagnostic agent is released from thejacket into the body lumen and thereby delivered at and around thelocation of the stent assembly within the body lumen.

The expanded jacket of biocompatible, non-thrombogenic expandablematerial such as heterologous tissue should extend over a substantialportion, preferably all, of the stenotic region in which it is disposedin order to minimize the restenosis.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1 is a perspective view, partially in section, of a stent assemblyof the invention showing the tubular, expandable, metallic stentpositioned coaxially within a cylindrical exterior jacket ofheterologous tissue;

FIG. 2 is an elevational view, partially in section, of a deliverycatheter having a jacketed stent mounted on an inflatable balloon on thedistal extremity of the catheter;

FIG. 3 is a transverse cross sectional view of the stent assembly shownin FIG. 1, taken along lines 3-3;

FIG. 4 is a perspective view, partially in section, of one embodiment ofthe stent assembly, shown in the expanded configuration, having abiocompatible non-thrombogenic jacket covering the length of theexpandable stent;

FIG. 5 is a transverse cross sectional view of one embodiment of thestent assembly prior to being expanded, illustrating the biocompatiblenon-thrombogenic jacket in a S-shaped folded configuration;

FIG. 6 is a transverse cross sectional view of another embodiment of thestent assembly prior to being expanded, illustrating the biocompatiblenon-thrombogenic jacket in a U-shaped folded configuration;

FIG. 7 is a perspective view, partially broken away, of one embodimentof the stent assembly having a biocompatible non-thrombogenic jacketcomprising an overlapping ribbon; and

FIG. 8 is transverse cross sectional view of one embodiment of the stentassembly prior to being expanded, having a biocompatiblenon-thrombogenic jacket in an overlapping wrapped configuration.

PREFERRED EMBODIMENTS OF THE INVENTION

The principles and uses of the teachings of the present invention may bebetter understood with reference to the accompanying description,figures and examples. In the figures, like reference numerals refer tolike parts throughout.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details set forth herein. The invention can be implemented withother embodiments and can be practiced or carried out in various ways.It is also understood that the phraseology and terminology employedherein is for descriptive purpose and should not be regarded aslimiting.

Generally, the nomenclature used herein and the laboratory proceduresutilized in the present invention include techniques from the fields ofbiology, chemistry, engineering and physics. Such techniques arethoroughly explained in the literature. Unless otherwise defined, alltechnical and scientific terms used herein have the same meaning ascommonly understood by one of ordinary skill in the art to which theinvention belongs. In addition, the descriptions, materials, methods,and examples are illustrative only and not intended to be limiting.Methods and materials similar or equivalent to those described hereincan be used in the practice or testing of the present invention. Allpublications, patent applications, patents and other referencesmentioned are incorporated by reference in their entirety as if fullyset forth herein. In case of conflict, the specification herein,including definitions, will control.

As used in the claims, the terms “comprising” and “including” orgrammatical variants thereof are to be taken as specifying the statedfeatures, integers, steps or components but do not preclude the additionof one or more additional features, integers, steps, components orgroups thereof. This term encompasses the terms “consisting of” and“consisting essentially of”.

As used in the claims, the phrase “consisting essentially of” orgrammatical variants thereof when used herein are to be taken asspecifying the stated features, integers, steps or components but do notpreclude the addition of one or more additional features, integers,steps, components or groups thereof but only if the additional features,integers, steps, components or groups thereof do not materially alterthe basic and novel characteristics of the claimed composition, deviceor method.

Herein the terms “framework” and “stent” are often used interchangeably,and refer to a substantially tubular expandable device known to oneskilled in the art as a stent. Further, herein the terms “jacket”.“stent jacket”, “cover” and “stent cover” are often used interchangeablyto refer to a substantially tubular stent jacket. Further, herein theterms “stent” and “stent assembly” are often used interchangeably torefer to a substantially tubular expandable device known to one skilledin the art as a stent associated with a jacket. From the context inwhich a given term is used, one skilled in the art is able to understandwhat is intended. In case of confusion, the reader is directed either toU.S. patent application Ser. No. 09/156,034 issued as U.S. Pat. No.6,254,627 or to U.S. patent application Ser. No. 08/935,784 issued asU.S. Pat. No. 6,468,300 for clarification.

As shown in FIG. 1, a stent assembly 10 of this invention generallycomprises a tubular, expandable metallic framework forming the stent 12positioned coaxially within a cylinder 14 of heterologous tissue.Preferably, metallic stent 12 extends about 1 mm beyond each end ofcylinder 14 to prevent prolapse of the tissue into the lumen of thestent when it is expanded. Cylinder 14 may be secured to metallicframework 12 by any suitable means. For example, four radially spacedsutures 16 may be placed at each end of cylinder 14.

Cylinder 14 preferably comprises bovine pericardium, a material shown toresist suture line bleeding, require no pre-clotting, supportendothelialization and have an excellent host-tissue response. Further,bovine pericardial tissue has an elasticity of up to about 30% whichallows the tissue cylinder to conform to both the unexpanded andexpanded configurations of the metallic framework with out adding agreat deal of bulk which increases the profile on the balloon. Otherheterologous tissue suitable in the practice of the invention includesporcine pericardium, equine pericardium, heterologous peritoneum,heterologous pleura, aortic leaflet and others. Useful heterologoustissue is relatively impenetrable, which prevents tissue build up andthe migration of smooth muscle cells through the stent framework. Aparticularly preferred bovine pericardium has cross-linked collagen andis available from Bio Vascular. Bovine pericardium tissue is availablein a thickness ranging from about 0.25 mm to about 0.75 mm, with anaverage of about 0.45 mm. Thicknesses of 0.45 mm and less are preferred,so long as the mechanical strength remains sufficient.

Metallic stent 12 may comprise any suitable conventional stent. Forexample, Micro Stent II, available from Arterial Vascular Engineering,and Multi-Link, available from Guidant, have proven useful. Other stentsthat may be used in the practice of this invention include thePalmaz-Shatz stent from Johnson and Johnson, the Gianturco stent fromCook Incorporated and other commercially available stents. Conventionalballoon expandable stents are preferred, but, as previously mentioned,self-expanding stents formed from shape memory materials are alsosuitable.

The cylinder of heterologous tissue 14, may be formed by cutting arectangle of tissue having a length about 2 mm shorter than the stent onwhich it is to be mounted and a width about equal to the circumferenceof the expanded stent. The two sides corresponding to the length of thestent then may be secured together, such as by sewing with 6-0 or 7-0polypropylene sutures 18. Other means for securing the sides of thestent cover together include mechanical means such as staples, adhesiveor chemical bonding and the like. It may be desirable to support thetissue while manipulating it. For example, a 9 French introducer dilatormay be used to support a 3 mm diameter cylinder, an 11 French dilatorfor a 3.5 mm cylinder and a 12 French dilator for a 4 mm cylinder. Thetissue should be kept wet at all times during manipulation.Additionally, radio-opaque markers, such as rings of gold or platinum,may be added to the outer layer of the tissue so that the integrity ofthe cylinder may be assured before deployment. The cylinder ofheterologous tissue is configured to be mounted onto a stent andgenerally has a length of about 5 to about 80 mm, preferably about 10 toabout 50 mm and a diameter of about 2 to about 6 mm preferably about 2.5to about 5 mm.

The use of the covered stent system generally follows conventionalprocedures. In particular, a guidewire is backloaded into a deliverycatheter having the covered stent assembly 10 loaded over an inflatableballoon or on a self expanding stent delivery system. The catheter andguidewire are percutaneously introduced by means of a conventionalSeldinger technique and a 9 or 10 French guiding catheter into thepatient's arterial system. The guidewire is advanced out deliverycatheter through the vasculature under fluoroscopic imaging until itcrosses a stenotic region. Then the catheter is advanced over theguidewire until the stent 10 is positioned at the desired locationwithin the stenotic region. Then, the balloon is inflated or thesecuring mechanism of the self expanding stent is released to expandmetallic framework 12 and tissue cylinder 14, seating the assemblywithin the vessel. The balloon is then deflated and the catheter isremoved, leaving the expanded stent assembly in place.

Also with reference to FIG. 1, stent assembly 10 comprises a tubular,expandable metallic framework forming the stent 12 with an exteriorjacket 14 of heterologous tissue. In the embodiment illustrated in FIG.1, metallic stent 12 extends about 1 mm beyond each end of jacket 14 toprevent prolapse of the tissue into the lumen of the stent when it isexpanded. Jacket 14 may be secured to metallic framework 12 by anysuitable means. For example, four radially spaced sutures 16 may beplaced at each end of jacket 14.

In a presently preferred embodiment of the stent assembly illustrated inFIG. 1, the jacket 14 contains a therapeutic or diagnostic agent, asshown in FIG. 3, illustrating a transverse cross section of the stentassembly shown in FIG. 1, taken along lines, 3-3.

Exterior jacket 14 preferably comprises bovine pericardium, a materialshown to resist suture line bleeding, require no pre-clotting, supportendothelialization and have an excellent host-tissue response. Further,bovine pericardial tissue has an elasticity of up to about 30% whichallows the tissue cylinder to conform to both the unexpanded andexpanded configurations of the stent 12 with out adding a great deal ofbulk which increases the profile on the balloon. Other heterologoustissue suitable in the practice of the invention includes porcinepericardium, equine pericardium, heterologous peritoneum, heterologouspleura, aortic leaflet, veins and arteries, and others. Usefulheterologous tissue is relatively impervious and impenetrable so as toprevent tissue build up and the migration of smooth muscle cells throughthe stent framework. A particularly preferred bovine pericardium hascross-linked collagen and is available from Bio Vascular. Bovinepericardium tissue is available in a thickness ranging from about 0.25mm to about 0.75 mm, with an average of about 0.45 mm.

In a presently preferred embodiment of the invention, the biocompatiblenon-thrombogenic jacket 14 has a thickness of less than about 0.25 mm,and preferably has a thickness of about 0.05 mm to about 0.20 mm, andmost preferably about 0.1 mm to about 0.15 mm. However, biocompatiblenon-thrombogenic jackets having a thickness of up to about 0.75 mm maybe used. In the embodiment of the invention in which a thinbiocompatible non-thrombogenic jacket having a thickness of less thanabout 0.25 mm is used, the heterologous tissue used to form the jacketis typically thinned before being assembled with the stent. The tissuemay be thinned by a variety of suitable methods including peeling,shaving or otherwise removing a thin layer of the tissue. In a presentlypreferred embodiment, the thin jacket comprises the serous pericardium,which is the smooth, inner layer of the pericardium, which has beenseparated from at least a part of the outer layer of the pericardium.Similarly, where other forms of heterologous tissue are used, such asveins or arteries, the venous or arterial walls may be thinned to thepresently preferred thickness of about 0.05 mm to about 0.20 mm. As aresult of being thinned, the jacket may have reduced elasticity, so thatthe thin jacket is preferably provided on the unexpanded stent in afolded or overlapping wrapped configuration which provides sufficientmaterial to cover the larger circumference of the expanded stent, aswill be discussed in greater detail below.

The biocompatible non-thrombogenic jacket 14 preferably has a lengthconfigured to cover the length of the expanded stent, as illustrated inFIG. 4, showing an expanded stent 12 with a jacket 14 extending thelength of the stent, with a length equal to the stent length. However,the jacket may have a length that is not equal to the length of thestent. For example, the jacket may have a length less than the stentlength, as illustrated in FIG. 1, preferably not more than about 10%-20%less than the length of the stent. However, the jacket may cover an evensmaller percentage of the length of the stent, as for example, when thestent assembly is used in a Transjugular Intrahepatic Portal Shunt(TIPS) application, where the jacket length is about 50% less than thelength of the stent. Alternatively, the jacket may have a length greaterthan the length of the stent, preferably not more than about 5% greaterthan the stent length. The jacket preferably has a circumference aboutequal to the circumference of the expanded stent, configured to fit onan inner or outer surface of the expanded stent. The jacket preferablyfits on the expanded stent so that the jacket conforms to the expandedstent without flaps of excess material.

Metallic stent 12 may comprise any suitable conventional stent. Forexample, Micro Stent II and GFX stents available from Arterial VascularEngineering, and Multi-Link, available from Guidant, have proven useful.Other stents that may be used in the practice of this invention includethe Palmaz-Shatz stent from Johnson and Johnson, the Gianturco stentfrom Cook Incorporated and other commercially available stents.Conventional balloon expandable stents are preferred, but, as previouslymentioned, self-expanding stents, such as those formed from shape memorymaterials, are also suitable.

The stent assembly is formed by covering a surface of the unexpandedstent with the heterologous tissue forming the jacket 14. In oneembodiment, the heterologous tissue is mounted onto the unexpanded stentin the form of a cylinder of tissue. The cylinder of heterologous tissueforming the jacket 14, may be formed by cutting a rectangle of tissuehaving a length about 2 mm shorter than the stent on which it is to bemounted and a width about equal to the circumference of the expandedstent. The two sides corresponding to the length of the stent then maybe secured together, such as by sewing with 6-0, 7-0, 8-0 or 10-0polypropylene sutures. Other means for securing the sides of the stentcover together include mechanical means such as staples, adhesive orchemical bonding and the like. It may be desirable to support the tissuewhile manipulating it. For example, a 9 French introducer dilator may beused to support a 3 mm diameter cylinder, an 11 French dilator for a 3.5mm cylinder and a 12 French dilator for a 4 mm cylinder. The cylinder oftissue having a circumference about equal to the circumference of theexpanded stent may be provided on the unexpanded stent in a folded orwrapped configuration. In one embodiment, the tissue on the unexpandedstent forms wings 30 on either side of the stent which are folded aboutstent, reducing the profile of the assembly, and unfolding uponexpansion of the stent. In the embodiment illustrated in FIG. 5, thewings are folded in the same direction in an S-shaped configuration. Inanother embodiment, illustrated in FIG. 6, the wings of the cylinder oftissue on the unexpanded stent are folded about stent in oppositedirections in a U-shaped configuration. However, the cylinder of tissuemay be placed about the unexpanded stent in a variety of suitableconfigurations, as for example, where the wings of the cylinder oftissue are collapsed toward the stent, such as in an accordion typeconfiguration (not shown). It would be apparent to one of skill in theart that the heterologous tissue forming the jacket could be foldedabout the unexpanded stent as outlined above whether or not the tissuehad been formed into a cylinder of tissue before mounting onto theunexpanded stent.

In another embodiment, the heterologous tissue is wrapped around theunexpanded stent, so that sufficient tissue to cover the expanded stentis provided. In one embodiment, illustrated in FIG. 7, a ribbon oftissue is spirally wrapped around the unexpanded stent down a lengththereof. The adjacent turns of the ribbon of tissue overlap, so that theribbon unwraps as the stent expands to provide the jacket 14 configuredto cover the expanded stent and having a circumference about equal tothe circumference of the expanded stent. Preferably, the ribbon oftissue is wrapped along the entire length of the stent. In anotherembodiment, a rectangle of tissue having a width about equal to thecircumference of the expanded stent on which it is to be mounted isrepeatably wrapped around the outer circumference of the unexpandedstent, so that multiple layers of tissue are present on at least a partof the unexpanded stent, as shown in FIG. 8, illustrating a transversecross section of an unexpanded stent with a wrapped jacket thereon.Preferably, one end of the tissue is fixed to the stent, and the tissueis then tightly wrapped around the stent. Upon expansion of the stent,the tissue unwraps to provide the jacket 14 having a circumference aboutequal to the circumference of the expanded stent. Preferably the lengthof the tissue is about equal to the length of the stent.

The tissue can be caused to remain in the folded or wrappedconfigurations until the stent is expanded by pressing the fluid out ofthe folded or wrapped tissue. Additionally, securing members such assurgical tape, ties, or breakable bands may be provided to releasablyhold the tissue in the folded or wrapped configurations.

Depending upon the jacket material, the tissue may be kept wet at alltimes during manipulation or it may be dry until advanced into thepatient's blood stream. Additionally, radio-opaque markers, such asrings of gold or platinum, may be added to the outer layer of the tissueso that the integrity of the cylinder may be assured before deploymentwithin the body lumen. The cylinder of heterologous tissue configured tobe mounted onto a stent and the jacket 14 formed by the cylinder oftissue or the unwrapped or unfolded tissue generally has a length, forcoronary applications, of about 4 to greater than about 80 mm, typicallyabout 5 to about 80 mm, preferably about 10 to about 50 mm, and adiameter of about 1.5 to about 35 mm, typically about 2 to about 6 mm,preferably about 2.5 to about 5 mm. The actual length and diameter ofthe cylinder of heterologous tissue may vary, and will depend on thenature of the vessel in which the stent assembly is implanted. Forexample, for peripheral vessel applications, such as an aortic abdominalaneurysm, a larger cylinder of heterologous tissue having a length ofabout 5 mm to about 200 mm and a diameter of about 2 mm to about 60 mmwould be used.

The jacketed stent assembly 10 is inserted into the body lumen in thefollowing fashion. A guidewire 20 is backloaded into a delivery catheter22 having the jacketed stent assembly 10 mounted over an inflatableballoon 24 on the distal extremity of the delivery catheter (asschematically shown in FIG. 2) or on a self expanding stent deliverysystem (not shown). The catheter 22 and guidewire 20 are percutaneouslyintroduced by means of a conventional Seldinger technique and a 5-9 or10 French guiding catheter (not shown) into the patient's arterialsystem. Larger guiding catheters, for example up to about 25 French, maybe used depending on the application. The guidewire 20 is advanced outdelivery catheter 22 through the vasculature under fluoroscopic imaginguntil it crosses a stenotic region. Then the catheter 22 is advancedover the guidewire 20 until the stent assembly 10 is positioned at thedesired location within the stenotic region. Then, the balloon 24 isinflated or the securing mechanism of the self-expanding stent isreleased to expand the stent 12 and cylindrical jacket 14, seating theassembly 10 within the vessel. The balloon 24 is then deflated and thecatheter 22 is removed, leaving the expanded stent assembly 10 in place.

Although primarily described with respect to preventing restenosis inangioplasty patients, the covered stents of this invention may be usedin a number of coronary artery, peripheral artery and non-vascularapplications. For example, coronary artery applications include use inectatic arteries and ectatic arteries containing an obstructive lesion,aneurismatic arteries, saphenous vein grafts and native arteriescoronary perforation, coronary fistula, and ostial coronary lesions.Peripheral artery applications include aortic abdominal aneurysm andother aneurismatic peripheral arteries, transjugular intrahepatic portalshunt, percutaneous transluminal angioplasty, fistula closing and neurointerventions (such as aneurysms and arterial-venous malformations),small vessel intraluminal grafting, and ostial renal artery lesions.Finally, the covered stents of this invention may be used in urological,gastroenterological, respiratory, neurological, and other non-vascularapplications. For example, urological field applications includeurethral stenting for stenosis due to tumors, fibrous tissue andperforation. Gastroenterological field applications include fistulaclosing, reconstruction such as esophagus reconstruction, and esophagealbleeding. Respiratory field applications include tracheal and bronchialobstructions, and neurological field applications include carotidangioplasty.

A general description of the device of the present invention as well asa preferred embodiment of the present invention has been set forthabove. One skilled in the art will recognize and be able to practicemany changes in many aspects of the device described above, includingvariations that fall within the teachings of this invention. It isappreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination. Although the invention has been describedin conjunction with specific embodiments thereof, it is evident thatmany alternatives, modifications and variations will be apparent tothose skilled in the art. Accordingly, the present invention is intendedto embrace all such alternatives, modifications and variations that fallwithin the spirit and broad scope of the appended claims. The spirit andscope of the invention should be limited only as set forth in the claimswhich follow.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention.

What is claimed is:
 1. A stent assembly, comprising: an expandable stentshaped as a hollow cylinder; and functionally associated with saidexpandable stent, a stent jacket comprising a thin serous membrane, themembrane comprising a smooth inner cell layer and a thin outer fibrouslayer, wherein said thin serous membrane has a thickness of about 0.05mm to about 0.20 mm, wherein the stent is positioned coaxially withinthe stent jacket.
 2. The stent assembly of claim 1, wherein said jacketis fit about an outer surface of said expandable stent.
 3. The stentassembly of claim 1, further comprising a therapeutic or diagnosticagent releasably contained within said stent jacket.
 4. The stentassembly of claim 1, wherein the thin serous membrane has a thickness ofabout 0.1 mm to about 0.15 mm.
 5. The stent assembly of claim 1, whereinthe stent jacket has a folded or overlapping wrapped configuration whenapplied to the stent.
 6. A method of producing the stent assembly ofclaim 1, comprising: providing a sheet of serous membrane, the membraneincluding a smooth inner cell layer and an outer fibrous layer; thinningsaid sheet of serous membrane by removing a portion of said outerfibrous layer thereby making a sheet of thinned serous membrane having athickness of about 0.05 mm to about 0.20 mm, wherein the thinned serousmembrane comprises cells; associating said sheet of thinned serousmembrane with an expandable stent shaped as a hollow cylinder, therebyproducing the stent assembly, wherein the stent is positioned coaxiallywithin the thinned serous membrane.
 7. The method of claim 6, whereinsaid thinning is effected by at least one method selected from the groupconsisting of peeling and shaving.
 8. The method of claim 6, whereinsaid associating includes wrapping said sheet about said expandablestent.
 9. The method of claim 6, further comprising: impregnating saidsheet of thinned serous membrane with a liquid containing a therapeuticor diagnostic agent.